Decreasing potential iatrogenic risks associated with influenza vaccines

Abstract

Influenza viruses for use in preparing human vaccines have traditionally been grown on embryonated hen eggs, although more modern techniques grow the virus in mammalian cell culture e.g. on Vero, MDCK or PER.C6 cell lines. The inventor has realised that the conditions used for influenza virus culture can increase the risk that pathogens other than influenza virus may grow in the cell lines and have identified specific contamination risks. Suitable tests can thus be performed during manufacture in order to ensure safety and avoid iatrogenic infections.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of U.S. patent application Ser. No. 11 / 662,481, filed Jul. 2, 2008, which is a U.S. National Phase patent application of PCT / IB2005 / 003266, filed Sep. 9, 2005, which claims priority to European Patent Office (EPO) patent application Serial No. 04255471.7, filed Sep. 9, 2004, all of which are hereby incorporated by reference in the present disclosure in their entirety.TECHNICAL FIELD[0002]This invention concerns the production and quality control of influenza virus vaccines.BACKGROUND ART[0003]Influenza viruses for use in preparing human vaccines have traditionally been grown on embryonated hen eggs, although more modern techniques grow the virus in mammalian cell culture e.g. on Vero cells, MDCK cells or PER.C6 cells. The change in virus growth substrate has provided an opportunity for regulatory re-assessment of influenza vaccine safety. For example, contamination with host cell DNA has been a regulator...

AI Technical Summary

Benefits of technology

The patent text describes a process for preparing influenza vaccines using mammalian cell lines instead of embryonated eggs. The use of mammalian cell lines has its own risks of contamination, but the inventor has identified specific risks and developed a process to test for and remove these contaminants. The process involves growing the influenza virus in a mammalian cell line and testing it for the presence of infectious agents that can grow in the cell line but not in embryonated eggs. The invention also provides an influenza vaccine that is free from certain infectious agents and can be tested for their presence using specific techniques. Overall, the invention provides a safer and more reliable process for preparing influenza vaccines.

Problems solved by technology

The inventor has realised that these conditions increase the risk that pathogens other than influenza virus may grow in the cell culture, thereby leading to potential contamination of the final vaccine product.

Tests for contamination are generally not difficult to perform, but a manufacturer first has to know what tests to perform.

Some of the contaminants may be harmless in a final vaccine product, but their presence can interfere with influenza virus propagation and downstream purification, and so their removal is primarily of concern for quality and reproducibility; other contaminants would be harmful in a final vaccine, and so their removal is primarily a safety concern.

Influenza viruses grown on cell culture are at particular risk from contamination because the strains used for vaccine production are changed every year, and so new cultures have to be established every year.

This annual change in production materials means that every new year brings a new risk of contamination, particularly as multiple passages are involved during preparation of seed viruses for manufacturers, thereby increasing the risk of parallel growth of adventitious pathogenic agents.

These infectious agents represent a new contamination risk for influenza vaccines that was never of concern for traditional influenza vaccines.

These infectious agents are thus a contamination risk only for certain influenza vaccines.